Iododerivative of pargyline: a potential tracer for the exploration of monoamine oxidase sites by SPECT

Monoamine oxidases are important in the regulation of monoaminergic neurotransmission. An increase in monoamine oxidase B (MAO B) has been observed in some neurodegenerative diseases, and therefore quantification of cerebral MAO B activity by SPECT would be useful for the diagnosis and therapeutic follow-up of these disorders. We have developed an iodinated derivative of pargyline, a selective inhibitor of MAO B, in order to explore this enzyme by SPECT. Stable bromo and iodo derivatives of pargyline were synthesized and chemically characterized. The radioiodinated ligand [125I]-2-iodopargyline was obtained with high specific activity from the bromo precursor by nucleophilic exchange. Affinity and selectivity of 2-iodopargyline were tested in vitro. Biodistribution study of [125I]-2-iodopargyline was performed in rats. Radioiodinated ligand were obtained in a no-carrier-added form. 2-iodopargyline has a higher in vitro affinity for MAO B than pargyline. However, the in vitro selectivity for MAO B was better for pargyline than for 2-iodopargyline. Ex vivo autoradiographic studies and in vivo saturation studies with selective inhibitors of MAO showed that the cerebral biodistribution of [125I]-2-iodopargyline in the rat is consistent with high level binding to MAO B sites in the pineal gland and in the thalamus. In conclusion, 2-iodopargyline preferentially binds in vivo to MAO B sites with high affinity. However, its selectivity for MAO B in rats is not very high, whereas this ligand binds to a lesser extent to MAO A. It will be then of great value to evaluate the specificity of 2-iodopargyline in humans. This new ligand labeled with 123I should therefore be a suitable tool for SPECT exploration of MAO B in the human brain.     

Una variazione del metodo di Halley

Sommario In questa nota si studia una classe di metodi iterativi, per la ricerca delle radici di una equazione, che include il metodo di Halley. Si prova che ogni metodo della classe è del terzo ordine e si calcola la costante di errore per ognuno di essi. Si individuano poi quei metodi della classe che sono globalmente convergenti per funzioni genus zero o uno. Infine is trova un metodo che ha una costante in valore assoluto più piccola di quella di Halley. Tale metodo è di tipo razionale e involge le stesse derivate di quello di Halley.

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We study a class of iterative methods devoted to the search of the roots of an equation. The class includes Halley's method. We prove each method belonging to the class to be of third order and for it evaluate the error constant. Among such methods we identify the ones which are globally convergent for zero or one genus functions. In particulary we find a method which has an error constant whose absolute value is less than the Halley's one. This is a rational one-point method which involves the same derivatives as Halley's method.

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Lavoro svolto nell'ambito del gruppo G.N.I.M.     

Structural study by 1H NMR of the first adducts of the telomerization of methylmethacrylate with thiophenol

The stereoselectivity of the different steps (addition step and transfer step) of the radical telomerization of methylmethacrylate with thiophenol has been determined by preparing and analyzing the first adducts by ¹H NMR analysis.     

Surjections and coverings

This paper determines the necessary and sufficient condition under which a collection of sequence covers on a finite set can be induced by a surjection. The relationship of sequence covers and surjections to generalized decomposition of an automaton allowing feedback, is the same as the relationship of partitions and bijections to series-parallel decompositions. The condition determined is a natural, but complex generalization of the known condition for the series-parallel case.     

Oligomerization and Nitration of the Grass Pollen Allergen Phl p 5 by Ozone,Nitrogen Dioxide,and Peroxynitrite: Reaction Products,Kinetics, and Health Effects

The allergenic and inflammatory potential of proteins can be enhanced by chemical modification upon exposure to atmospheric or physiological oxidants. The molecular mechanisms and kinetics of such modifications, however, have not yet been fully resolved. We investigated the oligomerization and nitration of the grass pollen allergen Phl p 5 by ozone (O₃), nitrogen dioxide (NO₂), and peroxynitrite (ONOO^–). Within several hours of exposure to atmospherically relevant concentration levels of O₃ and NO₂, up to 50% of Phl p 5 were converted into protein oligomers, likely by formation of dityrosine cross-links. Assuming that tyrosine residues are the preferential site of nitration, up to 10% of the 12 tyrosine residues per protein monomer were nitrated. For the reaction with peroxynitrite, the largest oligomer mass fractions (up to 50%) were found for equimolar concentrations of peroxynitrite over tyrosine residues. With excess peroxynitrite, the nitration degrees increased up to 40% whereas the oligomer mass fractions decreased to 20%. Our results suggest that protein oligomerization and nitration are competing processes, which is consistent with a two-step mechanism involving a reactive oxygen intermediate (ROI), as observed for other proteins. The modified proteins can promote pro-inflammatory cellular signaling that may contribute to chronic inflammation and allergies in response to air pollution.     

Pilot-scale Studies of Different Covers on Unoxidised Sulphide-rich Tailings in Northern Sweden: the Geochemistry of Leachate Waters

Abstract.  Leachate water quality from covered and uncovered unoxidised sulphide-rich tailings in six pilot-scale (5x5x3 m³) test cells was monitored during 2004 and 2005. The covers consisted of a layer of clayey till, sewage sludge, apatite or Trisoplast (a commercial mixture of tailings, bentonite, and a polymer). All layers were protected by an unspecified till except in one reference cell, where the tailings were left open. All leachate waters showed near-neutral pH as a result of neutralization by calcite in the tailings and by Ca(OH)₂ added prior to deposition. Average dissolved sulphur concentrations in the leachates were ≈ 600 mg L^-1, except in the cell with sewage sludge (300 mg L^-1). The source of sulphur was mainly pyrite oxidation, but residual sulphur probably remained from the enrichment process. The near-neutral pH favoured precipitation of metal-(oxy)hydroxides with subsequent removal of trace elements such as Cd, Cu and Pb (< 15 μg L^-1) from the solutions. High concentrations of Co, Mn, Ni, and Zn were found in leachates from the apatite, Trisoplast, and uncovered tailings cells. High As concentrations were found in the leachates in the sewage sludge and clayey till cells. The lowest metal concentrations, redox potential, and highest pH were found in the sewage sludge cell. Decreased elemental metal concentrations during 2004 suggest improved performance over time.     

Modelling of Specific Moisture Extraction Rate and Leakage Ratio in a Condensing Tumble Dryer

The use of tumble dryers in households is becoming more common. Tumble dryers, however, consume large amounts of electric energy. A statistical model over the tumble dryer is created from a design of experiments. The model will be used to find the best settings for the power supply to the heater, the internal airflow and the external airflow in order to reach a high specific moisture extraction rate (SMER) and a low leakage ratio of water vapour. The aim also involves explaining the trends of the SMER and the leakage ratio based on the physics of the tumble dryer drying process. A statistically significant model, which can be used for improving the SMER and leakage ratio, was established from 19 experiments in a condensing tumble dryer. The results show that a high power supply to the heater, a high internal airflow and a low external airflow give the highest SMER values. This combination of settings also results in the largest leakage ratio values for the dryer. Leakage is most affected by the external airflow.